Eli Lilly and Company has announced positive topline results from the Phase-III BRUIN CLL-313 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton Tyrosine Kinase (BTK) inhibitor, versus chemoimmunotherapy (bendamustine plus rituximab), in treatment-naïve patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) without 17p deletions. The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in Progression-Free Survival (PFS) compared to chemoimmunotherapy, as assessed by an Independent Review Committee (IRC), indicating one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study.

Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but was trending strongly in favour of Pirtobrutinib, and will be tested for statistical significance at the time of the primary OS analysis, which is anticipated to occur in 2026. The overall safety profile of Pirtobrutinib in BRUIN CLL-313 was generally consistent with previously reported trials across treatment settings.

Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. The results from the BRUIN CLL-313 and BRUIN CLL-314 studies will form the basis for seeking label expansions in earlier lines of therapy, with global regulatory submissions beginning later this year.

"The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the potential of Pirtobrutinib to be a meaningful treatment option for people with untreated CLL/SLL. With this third positive Phase-III study, we continue to build the clinical evidence supporting the possible role of Pirtobrutinib in a variety of CLL/SLL treatment settings, including treatment-naïve, BTK inhibitor-naïve and BTK inhibitor exposed. We look forward to presenting these data, as well as data from the recently announced positive BRUIN CLL-314 study, at upcoming medical meetings and preparing global regulatory submissions, with the goal of making Pirtobrutinib an option for a wider group of patients who might benefit,” said Jacob Van Naarden, Executive Vice President and President, Lilly Oncology.

These data build on the previously reported positive results from the BRUIN Phase-I/II trial, the Phase-III BRUIN CLL-321 trial, the first randomised, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population, and the Phase-III BRUIN CLL-314 trial, the first-ever head-to-head Phase-III trial versus Ibrutinib in CLL to include treatment-naïve patients.